Details of the Drug

General Information of Drug (ID: DMIM5AP)

Drug Name
TAK-875
Synonyms
TAK-875; Fasiglifam; 1000413-72-8; TAK875; TAK 875; UNII-GLP1W4JXAH; GLP1W4JXAH; (S)-2-(6-((2',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid; CHEMBL1829174; [(3s)-6-({2',6'-Dimethyl-4'-[3-(Methylsulfonyl)propoxy]biphenyl-3-Yl}methoxy)-2,3-Dihydro-1-Benzofuran-3-Yl]acetic Acid; 3-Benzofuranacetic acid, 6-[[2',6'-diMethyl-4'-[3-(Methylsulfonyl)propoxy][1,1'-biphenyl]-3-yl]Methoxy]-2,3-dihydro-, (3S)-; J-501277
Indication
Disease Entry ICD 11 Status REF
Type-2 diabetes 5A11 Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 524.6
Logarithm of the Partition Coefficient (xlogp) 4.7
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C29H32O7S
IUPAC Name
2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid
Canonical SMILES
CC1=CC(=CC(=C1C2=CC=CC(=C2)COC3=CC4=C(C=C3)[C@@H](CO4)CC(=O)O)C)OCCCS(=O)(=O)C
InChI
InChI=1S/C29H32O7S/c1-19-12-25(34-10-5-11-37(3,32)33)13-20(2)29(19)22-7-4-6-21(14-22)17-35-24-8-9-26-23(15-28(30)31)18-36-27(26)16-24/h4,6-9,12-14,16,23H,5,10-11,15,17-18H2,1-3H3,(H,30,31)/t23-/m1/s1
InChIKey
BZCALJIHZVNMGJ-HSZRJFAPSA-N
Cross-matching ID
PubChem CID
24857286
CAS Number
1000413-72-8
DrugBank ID
DB12491
TTD ID
D0V1WQ
INTEDE ID
DR1882
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Free fatty acid receptor 1 (GPR40) TTB8FUC FFAR1_HUMAN Modulator [2]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [3]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [3]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Substrate [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Gene/Protein Processing [4]
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Gene/Protein Processing [5]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Gene/Protein Processing [5]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Gene/Protein Processing [5]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Gene/Protein Processing [6]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Gene/Protein Processing [4]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Gene/Protein Processing [6]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Gene/Protein Processing [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Type-2 diabetes
ICD Disease Classification 5A11
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Free fatty acid receptor 1 (GPR40) DTT FFAR1 6.14E-01 -0.08 -1.33
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 8.58E-01 -3.73E-03 -1.00E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 2.76E-01 -4.64E-01 -9.16E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6484).
2 Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial. Diabetes Obes Metab. 2015 Jul;17(7):675-81.
3 Disposition and metabolism of the G protein-coupled receptor 40 agonist TAK-875 (fasiglifam) in rats, dogs, and humans. Xenobiotica. 2019 Apr;49(4):433-445.
4 Fasiglifam (TAK-875) Alters Bile Acid Homeostasis in Rats and Dogs: A Potential Cause of Drug Induced Liver Injury. Toxicol Sci. 2017 May 1;157(1):50-61. doi: 10.1093/toxsci/kfx018.
5 Fasiglifam (TAK-875): Mechanistic Investigation and Retrospective Identification of Hazards for Drug Induced Liver Injury. Toxicol Sci. 2018 Jun 1;163(2):374-384. doi: 10.1093/toxsci/kfx040.
6 Mechanistic investigations of the liver toxicity of the free fatty acid receptor 1 agonist fasiglifam (TAK875) and its primary metabolites. J Biochem Mol Toxicol. 2019 Aug;33(8):e22345. doi: 10.1002/jbt.22345. Epub 2019 May 8.